High Prevalence of Mental Health Disorders in Adolescents and Youth Living with HIV: An Observational Study from Eight Health Services in Sofala Province, Mozambique.

Adolescent mental health (MH) is a significant global health concern, which is extremely relevant when referring to adolescents and youth living with HIV (AYHIV). In Mozambique, ∼52% of the population is <18 years and the country has the world's eighth highest HIV prevalence (insert citation). We performed an observational study to evaluate anxiety, depression, post-traumatic stress disorder (PTSD) and alcohol-drug abuse in adolescents and youth assessing health services in Sofala Province, Mozambique. From November 20, 2019, to November 20, 2021, all adolescents and youth (10-24 years) accessing one of the psychological services offered at 8 Servicios Amigos dos Adolescentes (SAAJ) of the Sofala Province were screened by a psychologist using the following standardized tools: Generalized Anxiety Disorder-7 (GAD-7) for anxiety, Patient Health Questionnaire-9 (PHQ-9) for depression, Primary Care PTSD Screen for DSM-5 (PC-PTSD-5) for PTSD, and Cut down, Annoyed, Guilty, and Eye-opener Adapted to Include Drugs (CAGE-AID) for alcohol-drug abuse. Overall, 2108 adolescents and youth were included in the study (63% female, median age: 19 years). Of them, 1096 (52%) were HIV positive. AYHIV had higher scores at the four tools tested and for concomitant MH disorders (GAD-7, PHQ-9, PTSD-5, and CAGE). The multivariable logistic regressions showed a greater probability to be GAD-7 > 10 for women, [adjusting odds ratio (AOR): 1.46, 95% confidence interval (CI): 1.01-2.10], for workers (AOR: 2.18, 95% CI: 1.12-4.23) and people living with HIV (AOR: 1.78, 95% CI: 1.25-2.54). Higher values of CAGE (≥2) and PTSD (≥3) seemed to be associated only with HIV-positive status (AOR: 4.87, 95% CI: 3.72-6.38 and AOR: 1.73, 95% CI: 1.28-237). These data further reinforce the urgent need for a global health policy action with focused intervention on MH in AYHIV patients.

Mozambican Adolescents and Youths during the COVID-19 Pandemic: Knowledge and Awareness Gaps in the Provinces of Sofala and Tete.

(1) Background: Mozambique has an average population age of 17 years and adolescents and youths have a pivotal role in SARS-CoV-2 pandemic control. (2) Methods: We conducted a cross-sectional study in order to assess the awareness and information needs with regard to COVID-19 among a sample of adolescents and youths from two different Mozambican provinces. (3) Results: Only 25% of adolescents and youths had a high level of awareness and only 543/2170 participants reported a high level of knowledge regarding COVID-19. In our multivariate model, significant predictors of reporting a high level of knowledge about COVID-19 include female sex (O.R. = 1.47; 95% confidence interval (CI) 1.23-2.89), having a house without a thatched roof (O.R. = 1.85; 95% CI 1.02-2.95) and HIV-positive status (O.R. = 1.56; 95% CI 1.36-2.87). (4) Conclusions: Our study highlights an important and relevant knowledge gap in adolescents and youths with respect to the COVID-19 pandemic. Involving young people and adolescents in the fight against SARS-CoV-2 is an essential strategy, especially in countries where the national average age is young, such as Mozambique, and where this epidemic can aggravate an already fragile health system.

Breakthrough Cancer Pain Clinical Features and Differential Opioids Response: A Machine Learning Approach in Patients With Cancer From the IOPS-MS Study.

PURPOSE: A large proportion of patients with cancer suffer from breakthrough cancer pain (BTcP). Several unmet clinical needs concerning BTcP treatment, such as optimal opioid dosages, are being investigated. In this analysis the hypothesis, we explore with an unsupervised learning algorithm whether distinct subtypes of BTcP exist and whether they can provide new insights into clinical practice. METHODS: Partitioning around a k-medoids algorithm on a large data set of patients with BTcP, previously collected by the Italian Oncologic Pain Survey group, was used to identify possible subgroups of BTcP. Resulting clusters were analyzed in terms of BTcP therapy satisfaction, clinical features, and use of basal pain and rapid-onset opioids. Opioid dosages were converted to a unique scale and the BTcP opioids-to-basal pain opioids ratio was calculated for each patient. We used polynomial logistic regression to catch nonlinear relationships between therapy satisfaction and opioid use. RESULTS: Our algorithm identified 12 distinct BTcP clusters. Optimal BTcP opioids-to-basal pain opioids ratios differed across the clusters, ranging from 15% to 50%. The majority of clusters were linked to a peculiar association of certain drugs with therapy satisfaction or dissatisfaction. A free online tool was created for new patients' cluster computation to validate these clusters in future studies and provide handy indications for personalized BTcP therapy. CONCLUSION: This work proposes a classification for BTcP and identifies subgroups of patients with unique efficacy of different pain medications. This work supports the theory that the optimal dose of BTcP opioids depends on the dose of basal opioids and identifies novel values that are possibly useful for future trials. These results will allow us to target BTcP therapy on the basis of patient characteristics and to define a precision medicine strategy also for supportive care.

Factors Influencing the Clinical Presentation of Breakthrough Pain in Cancer Patients.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience.

Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.

Breakthrough Cancer Pain: Preliminary Data of The Italian Oncologic Pain Multisetting Multicentric Survey (IOPS-MS).

INTRODUCTION: An ongoing national multicenter survey [Italian Oncologic Pain multiSetting Multicentric Survey (IOPS-MS)] is evaluating the characteristics of breakthrough cancer pain (BTP) in different clinical settings. Preliminary data from the first 1500 cancer patients with BTP enrolled in this study are presented here. METHODS: Thirty-two clinical centers are involved in the survey. A diagnosis of BTP was performed by a standard algorithm. Epidemiological data, Karnofsky index, stage of disease, presence and sites of metastases, ongoing oncologic treatment, and characteristics of background pain and BTP and their treatments were recorded. Background pain and BTP intensity were measured. Patients were also questioned about BTP predictability, BTP onset (≤10 or >10 min), BTP duration, background and BTP medications and their doses, time to meaningful pain relief after BTP medication, and satisfaction with BTP medication. The occurrence of adverse reactions was also assessed, as well as mucosal toxicity. RESULTS: Background pain was well controlled with opioid treatment (numerical rating scale 3.0 ± 1.1). Patients reported 2.5 ± 1.6 BTP episodes/day with a mean intensity of 7.5 ± 1.4 and duration of 43 ± 40 min; 977 patients (65.1%) reported non-predictable BTP, and 1076 patients (71.7%) reported a rapid onset of BTP (≤10 min). Higher patient satisfaction was reported by patients treated with fast onset opioids. CONCLUSIONS: These preliminary data underline that the standard algorithm used is a valid tool for a proper diagnosis of BTP in cancer patients. Moreover, rapid relief of pain is crucial for patients' satisfaction. The final IOPS-MS data are necessary to understand relationships between BTP characteristics and other clinical variables in oncologic patients. FUNDING: Molteni Farmaceutici, Italy.

Switching to low-dose oral prolonged-release oxycodone/naloxone from WHO-Step I drugs in elderly patients with chronic pain at high risk of early opioid discontinuation.

PURPOSE: Chronic pain has a high prevalence in the aging population. Strong opioids also should be considered in older people for the treatment of moderate to severe pain or for pain that impairs functioning and the quality of life. This study aimed to assess the efficacy and safety of the direct switch to low-dose strong opioids (World Health Organization-Step III drugs) in elderly, opioid-naive patients. PATIENTS AND METHODS: This was a single-center, retrospective, observational study in opioid-naive patients aged ≥75 years, with moderate to severe chronic pain (>6-month duration) and constipation, who initiated treatment with prolonged-release oxycodone/naloxone (OXN-PR). Patients were re-evaluated after 15, 30, and 60 days (T60, final observation). Response to treatment was defined as an improvement in pain of ≥30% after 30 days of therapy without worsening of constipation. RESULTS: One-hundred and eighty-six patients (mean ± SD age 80.7±4.7 years; 64.5% women) with severe chronic pain (mean average pain intensity 7.1±1.0 on the 11-point numerical rating scale) and constipation (mean Bowel Function Index 64.1±24.4; 89.2% of patients on laxatives) were initiated treatment with OXN-PR (mean daily dose 11.3±3.5 mg). OXN-PR reduced pain intensity rapidly and was well tolerated; 63.4% of patients responded to treatment with OXN-PR. At T60 (mean daily OXN-PR dose, 21.5±9.7 mg), the pain intensity was reduced by 66.7%. In addition, bowel function improved (mean decrease of Bowel Function Index from baseline to T60, -28.2, P<0.0001) and the use of laxatives decreased. Already after 15 days and throughout treatment, ~70% of patients perceived their status as much/extremely improved. Only 1.6% of patients discontinued treatment due to adverse events. CONCLUSION: Low-dose OXN-PR in elderly patients naive to opioids proved to be an effective option for the treatment of moderate to severe chronic pain. Large-scale trials are needed to improve clinical guidance in the assessment and treatment of pain in older people.

Retrospective Evaluation of a Fixed-Dose Combination of Oxycodone and Acetaminophen to Manage Moderate Pain: The Lower the Better.

INTRODUCTION: Oxycodone is one of the most commonly used opioid analgesics in the clinical management of pain. The present retrospective analysis aimed to determine the dose of oxycodone that could achieve effective control of moderate pain when combined with a fixed dose of acetaminophen, and the time required to reach a clinically relevant reduction in intensity of pain. METHODS: Data of patients treated with a combination of oxycodone (5, 10, and 20 mg) and acetaminophen (325 mg) were evaluated for gender, current disease condition, basal pain intensity, total daily dose, days of controlled pain at the initial low dose, and pain intensity after treatment using a numeric pain rating scale. RESULTS: Data from a total of 491 patients were assessed; of these 93.5% of patients experienced persistent non-cancer pain and had an average baseline pain score of 5.68 ± 1.35. For the overall population, the pain score was reduced to 2.49 ± 1.71 with a mean dose of 8.68 ± 4.96 mg oxycodone after 21.60 ± 6.12 days of treatment with the combination. Almost 97% of the patients who reported relief of pain received 1.61 ± 0.67 doses of oxycodone 5 mg combined with 325 mg of acetaminophen. CONCLUSION: A low-dose combination of oxycodone with acetaminophen can be effective in the management of moderate pain and may help in reducing the treatment-associated adverse reactions and drug dependence. FUNDING: Sponsorship for article processing charges was provided by Molteni Farmaceutici, Florence, Italy.

Should the General Practitioner Consider Mesotherapy (Intradermal Therapy) to Manage Localized Pain?

Wide variations in the types of pain and response to analgesic pharmacotherapy mean that a variety of treatment strategies are needed. One approach is mesotherapy (intradermal therapy). This consists of microinjections into the skin and is ideally suited to the management of localized pain. Advantages include increasing the duration of drug activity, reduced risk of adverse events and interactions, and possible synergy with other therapies. Mesotherapy provides general practitioners with another tool for the treatment of local pain. However, it is important to provide patients with full details of the pros and cons of this approach and obtain informed patient consent.

Efficacy and tolerability of oral oxycodone and oxycodone/naloxone combination in opioid-naïve cancer patients: a propensity analysis.

BACKGROUND: World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. METHODS: Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. RESULTS: Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60 days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0-20.4 mg/d for OXY and 11.5-22.0 mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30 days and 60 days in OXN recipients (-16, P<0.0001 and -3.5, P=0.02, respectively); BFI worsened in the OXY group. The overall incidence of drug-related adverse events was 28.9% in the OXY group and 8.2% in the OXN group (P<0.01); nausea and vomiting were two to five times less frequent with OXN. Quality of life improved to a significantly greater extent in patients receiving OXN compared to OXY (increase in Short Form-36 physical component score of 7.1 points vs 3.2 points, respectively; P<0.001). CONCLUSION: In patients with chronic cancer pain, OXN provided analgesic effectiveness that is similar to OXY, with early and sustained benefits in tolerability. The relationship between responsiveness to OXN and clinical characteristics is currently being investigated.

Preventing and managing herpes zoster: key actions to foster healthy aging.

Population aging is the demographic phenomenon characterizing all countries in the world, and it is challenging the national infrastructures, in particular health systems. However, aging itself is not associated with increased medical spending, but disability and comorbidity that affect older individuals are the actual drivers for health expenditures. Therefore, if people age in better health, medical spending may be significantly reduced. Preventative interventions proved to be effective in reducing/preventing disease and disability and often found to be cost effective, include diet and exercise interventions, medications, routine disease screenings, and immunizations. Vaccination can protect older citizens against life-threatening diseases, such as influenza, pneumococcal infections, tetanus, and against diseases which adversely impact their quality of life, such as herpes zoster (HZ). Including HZ vaccination in its citizens' lifetime immunization calendar can reinforce Europe's commitment toward active, healthy aging. This paper outlines the consensus statement of a group of Italian experts on HZ.

Italian Oncological Pain Survey (IOPS): a multicentre Italian study of breakthrough pain performed in different settings.

OBJECTIVE: A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). METHODS: A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. RESULTS: 1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. CONCLUSION: This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient's quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics.

Open questions in the treatment of cancer pain: time for a strong evidence-based approach?

Pain affects patients with cancer at any stage of their disease. Yet, it is not adequately treated in a significant percentage of cases. In 1986, the WHO proposed a three-step approach for the treatment of pain in cancer patients (from nonopioids to weak opioids to strong opioids, according to pain intensity) following the recommendations of an international group of experts. The application of the WHO strategy demonstrated that a clear and simple approach is of educational value and ensured worldwide dissemination. However, there is little evidence that the WHO approach is the best, and there are still several points to debate on the treatment of cancer pain.

Reducing the burden of Herpes Zoster in Italy.

Herpes Zoster (HZ) is a viral disease with painful neuro-dermatologic manifestations. Incidence increases with age. In Italy, the estimated incidence is 6.3 cases/1000 person/year; hospital admissions are less than 2%, 69% in patients aged over 65 years. The most frequent complication of HZ is Post-Herpetic Neuralgia (PHN) characterized by metameric pain, allodynia, and hyperalgesia. In Italy 20.6% and 9.2% of HZ patients experience PHN after 3 and 6 months, respectively. Available antiviral and analgesic treatments are relatively unsatisfactory in reducing pain and length of the disease. Prevention has recently become possible with the live attenuated vaccine Oka/Merck. Clinical studies show a reduction of 51% in the incidence of the disease, 61% of its burden and 67% of PHN in vaccinees. Protection seems to be long lasting and vaccine safety matches registration requirements. Available evidence suggests that the costs for QALY (less than € 20 000) and avoided cases is favorable. Due to the heavy burden of disease, it is time to offer this vaccination to elderly population.

One-year follow-up of patients with long-lasting post-herpetic neuralgia.

BACKGROUND: Recent information on epidemiology and management of post-herpetic neuralgia (PHN), a painful complication of zoster, is scarce. METHODS: This study was conducted at the Pain Clinic of the Policlinico Tor Vergata, Rome, Italy, on eighty-five immunocompetent patients with a clinical diagnosis of PHN. At enrollment (time 0, T0), the patients were interviewed by physicians to obtain demographic data and information about their zoster clinical history and underwent a blood test for VZV-DNA research. DN4 and SF-12 questionnaires were used to assess the neuropathic nature of pain and the overall health status, respectively. A one-year follow-up was planned for enrolled cases, who were visited at regular intervals of at least 3 months. RESULTS: At T0 all the patients were at least 6 months from the episode of acute zoster and still presented with intense pain (mean VAS =6.7; mean DN4 = 5.7). Using antivirals within 72 hours from the rash onset was associated to a significant reduction of pain at T0 (p = 0.006 vs untreated patients). Only 2.6% of patients treated with antivirals during acute zoster but 18.6% of the untreated ones presented with neuropathic pain at T12 (p =0.007), even though the two groups were similar at T0. VZV-DNA was found in 5 out of the 50 available blood samples. At the last follow-up visit, PCS and MCS scores of the PHN patients were found to be recovered over those of the historical age-matched healthy controls. Undesirable side effects of analgesic therapies were observed in 15.3 to 28.8% of the patients. CONCLUSIONS: Patients who six months after acute zoster still have significant neuropathic pain, have a high probability of suffering from chronic pain in the subsequent months/years. The initial antiviral treatment has a significant impact on the pain. Current strategies of analgesic therapy are effective to achieve relief of pain in PHN patients, but they are burdened with heavy and undesirable side effects.

Breakthrough pain in patients with controlled or uncontrolled basal pain: an observational study.

BACKGROUND: Breakthrough pain (BTP) is traditionally defined as a pain exacerbation in patients with chronic controlled pain. However, this definition has recently been challenged. OBJECTIVES: To evaluate the prevalence of unsatisfactory control in patients with chronic cancer pain, and investigate the frequency and intensity of BTP episodes. METHODS: A total of 665 patients with chronic cancer pain attending 21 pain therapy units in Italy were evaluated for baseline pain intensity and number of BTP episodes over a 30-day period. All patients started, continued or modified treatment for BTP at enrollment, according to medical judgment. RESULTS: The number of BTP events was higher in patients with uncontrolled baseline pain, although the intensity and duration of episodes were similar. In patients with uncontrolled baseline pain, the number of events decreased with time and reached values comparable with those reported in patients with controlled pain. Both the intensity of the pain and the duration of the BTP events exhibited similar values in the two groups at all time points, following increased monitoring and the prescription of analgesic medication. CONCLUSION: Patients with uncontrolled baseline pain experienced BTP flares with higher frequency, but similar intensity and duration with respect to patients with controlled pain at baseline. Notably, a close follow-up and adequate management of the BTP episodes led to an improvement of BTP in the observed patients.

Long-term efficacy of OROS® hydromorphone combined with pregabalin for chronic non-cancer neuropathic pain.

BACKGROUND AND OBJECTIVES: Treatment for chronic non-cancer neuropathic pain can be complicated by side effects and drug interactions. Combining opioid analgesics and calcium channel modulators may overcome these and improve efficacy. The objective of the present study was to evaluate the efficacy and safety of OROS® hydromorphone combined with pregabalin in patients with chronic non-cancer neuropathic pain. METHODS: This retrospective observational study was conducted on clinical records from patients aged ≥18 years with chronic non-cancer neuropathic [>4 on the Douleur Neuropathique en 4 questions (DN4) scale] pain of ≥6 months duration, with severe intensity [>4 on the Numerical Rating Scale (NRS); range 0-10], who attended all visits and had ≥12 months of follow-up at the Tor Vergata University Polyclinic Hospital, from November 2008 to February 2011. Patients received an oral combination of OROS® hydromorphone and pregabalin. Pain was evaluated at each visit (months 1, 3, 6, 9, and 12) using the NRS and DN4 scale; Patients' Global Impression of Change (PGIC) was administered at months 1, 6, and 12. Dosage and side effects were recorded at each visit. RESULTS: Of 1,292 patients (32 % men, mean ± SD age 67.6 ± 11.9 years), 1,126 attended all visits. Seventeen percent (n = 224) had purely neuropathic pain. Initial mean dosage was 6.06 ± 2.00 mg/day for OROS® hydromorphone, 113.02 ± 21.94 mg/day for pregabalin. Dosages increased up to month 6, and returned to near initial dosages at month 12 (range 4-120 mg/day for OROS® hydromorphone; 75-600 mg/day for pregabalin). NRS pain scores (mean ± standard deviation) were 7.25 ± 1.34 at baseline and 1.85 ± 1.36 at 12 months (p < 0.0001); DN4 scores were 6.19 ± 1.65 at baseline, reduced to 1.84 ± 1.25 at 12 months (p < 0.0001), reductions of 74.4 and 70.2 %, respectively. More than 90 % of patients had a ≥50 % score reduction on both scales after 12 months. The PGIC scale showed that >75 % of patients felt improvement at 1 month, increasing to 91 % and 93 % at 6 and 12 months. The incidence of side effects was similar between elderly (aged >65 years) and younger subjects; there were no cases of addiction. CONCLUSIONS: The OROS® hydromorphone and pregabalin combination was efficacious for chronic non-cancer neuropathic pain and well tolerated, providing significant pain reduction without the risk of addiction and with a good tolerability profile, regardless of age.

Beyond the traditional definition of breakthrough pain: an observational study.

INTRODUCTION: Breakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions. METHODS: This was a prospective, non-interventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (<3 months) or chronic (>3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form. The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) non-chronic non-oncological pain. The correlation between BTP and gender was also investigated. RESULTS: Of 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P < 0.001). No differences were reported in terms of number and severity of daily BTP episodes. BTP was more frequent in females with non-oncological pain (P = 0.04). Females had a significantly higher pain severity (P = 0.02) than males. CONCLUSION: BTP is frequently reported in patients who do not have BTP according to the traditional definition. BTP frequency and severity is similar in oncological and non-oncological pain.

Prolonged-release oxycodone/naloxone in nonmalignant pain: single-center study in patients with constipation.

INTRODUCTION: Opioid treatment for chronic malignant and nonmalignant pain of moderateto-severe intensity is associated with bowel dysfunction leading to constipation; this often requires opioid dose reduction or interruption. Combination opioid agonist/antagonist therapy can restore normal bowel function. A prolonged-released (PR) fixed-dose combination of oxycodone and naloxone has been developed and efficacy has been demonstrated in phase 3 clinical trials. METHODS: This 2-month, retrospective, singlecenter, observational study assessed the effectiveness and safety of PR oxycodone/naloxone in consecutive nononcological patients with constipation and chronic pain despite analgesic treatment; specific subgroup analyses were performed in opioid-experienced or opioid-naïve patients and in age subgroups. Efficacy was assessed by: intensity of pain; bowel function; effective oxycodone/naloxone dose; Patients' Global Impression of Change (PGIC) scale; rescue paracetamol; and laxative use. Safety evaluations were also performed. RESULTS: Of 1,051 patients starting on the oxycodone/naloxone combination (32.0% male; mean age 67 ± 13 years, 53.9% opioid naïve), 1,012 completed 2 months of treatment. Overall, PR oxycodone/naloxone was associated with a significant decrease in pain intensity (P < 0.001), a reduced need for rescue paracetamol (P < 0.001), and PGIC score of "very much improved" or "much improved" in 84.0% of patients. Constipation markedly decreased (P < 0.001) despite reduced laxative use (P < 0.001 vs. baseline). The most frequent treatment-emergent adverse events were somnolence (2.0%), dizziness (1.1%), and confusion (1.0%). Clinical differences in endpoints were seen between opioid-naïve and opioid-experienced patients, and among agestratified groups, but efficacy was similar to the overall population. CONCLUSIONS: Fixed combination PR oxycodone/naloxone was effective and well tolerated in moderate-to-severe chronic pain in patients with constipation, providing analgesia and relief from bowel dysfunction. Consistent efficacy across patient subgroups provides guidance for daily management of chronic pain when therapy options are limited due to bowel dysfunction, regardless of age or previous medication. Supplementary material belonging to this paper is available on SpringerLink.

Palmitoylethanolamide in the treatment of chronic pain caused by different etiopathogenesis.

OBJECTIVE: To assess the efficacy and safety of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamines family, in reducing pain severity in patients with pain associated to different pathological conditions. METHODS: This was an observational study conducted on 610 patients who were unable to effectively control chronic pain with standard therapies. PEA (600 mg) was administered twice daily for 3 weeks followed by single daily dosing for 4 weeks, in addition to standard analgesic therapies or as single therapy. The primary outcome measure was the mean score pain severity evaluated by the numeric rating scale. Safety was also evaluated. RESULTS: PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects. CONCLUSIONS: In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions.